We propose to study the effects of ethanol on the properties of synaptic ionic channels in voltage clamped tissue cultured nerve and muscle using single channel recording techniques. We will study in detail the effects of aliphatic alcohols and general anesthetic agents on the single channel properties of the nicotinic endplate receptor in order to derive kinetic parameters for agonist assocation-dissociation reactions and the channel opening and closing reactions. In addition, we will attempt to measure the stoicheiometry of the alcohol or anesthetic binding to the channel. Using single channel recordings we will examine the kinetic and conductance properties of other chemically activated ionic channels in tissue cultured neurons investigating whether or not there is a characteristic pharmacological sensitivity to ethanol with respect to cell type, and whether or not all chemically activated synaptic channels respond to ethanol in a functionally similar manner. Single channel responses in both nerve and muscle will be measured in cells grown in the continuous presence of ethanol. These studies will provide insight into the question of the mechanism and time course of the development of ethanol tolerance at a molecular level. Finally, the effects of ethanol on the phenomenon of receptor "desensitization" in tissue cultured muscle cells will be examined using macroscopic iontophoretic techniques as well as single channel recordings.